Salt Supplement Restores the Gut Microbiome’s Anti-Aging Effects, New Swiss Study Shows

Highlights

• A harmful metabolite produced by gut bacteria increases with age in humans. 
• The metabolite induces cardiovascular dysfunction in mice, which can be mitigated with compounds called senolytics. 
• Sodium acetate also mitigates cardiovascular dysfunction while elevating NAD+ levels and activating longevity-associated sirtuin enzymes. 

What makes the microbes living in our gut — our gut microbiome — so important? Scientists in Switzerland have recently published the results of a study exploring the effects of the gut microbiome on aging, revealing that Clostridium, a type of gut bacteria, may contribute to the deterioration of our cardiovascular system. The findings are particularly relevant, as cardiovascular deterioration underlies cardiovascular disease (CVD), the leading cause of death worldwide. Fortunately, the findings suggest that steps can be taken to mitigate this deadly disease.

Harmful Gut Bacteria Molecule Increases with Age in Humans.  

As we age, our gut microbiome becomes altered for the worse, as harmful gut bacteria grow in abundance. These bacteria are harmful because they produce metabolites that contribute to chronic diseases. One such metabolite is called phenylacetic acid (PAA), which previous studies have linked to CVD. 

With this in mind, researchers from the University of Zurich, led by Jürg H. Beer, MD, sought to elucidate the link between PAA and CVD by first measuring it in mice and humans. They found that aged mice have higher levels of PAA than young mice. Moreover, a similar trend was shown in humans, whereby increased age was correlated with higher circulating PAA levels. Further experiments revealed that the high PAA levels were linked to Clostridium, suggesting that this harmful gut bacteria increases with age and produces PAA, which is then absorbed into the bloodstream. 

Senolytics Counter Bacteria-Induced Cardiovascular Deterioration  

To determine the role of Clostridium in CVD, Dr. Jürg H. Beer and his team examined the aorta of mice harboring an abundance of Clostridium in their gut. It was found that the Clostridium rendered this largest of arteries dysfunctional, as it exhibited reduced blood vessel formation (angiogenesis) capacity. Furthermore, the aorta contained elevated levels of senescent cells, which are cells that accumulate with age and are linked to age-related diseases like CVD. 

For this reason, the researchers employed senolytics, compounds that selectively eliminate senescent cells. Specifically, they used the senolytic combo dasatinib and quercetin (D+Q). The results showed that treating the Clostridium-harboring mice with D+Q reduced both aortic dysfunction and senescence, suggesting that senescent cells contribute to Clostridium-mediated cardiovascular deterioration. Moreover, PAA also triggered aortic senescence and dysfunction, suggesting that Clostridium promotes CVD by secreting PAA. 

Sodium Acetate Reduces Senescence and Cardiovascular Deterioration  

Illustrating the age-related worsening of the gut microbiome, beneficial gut bacteria like Prevotella and Rikenellaceae have to been shown to deplete with aging, which has been linked to CVD. Probiotics like Prevotella and Rikenellaceae produce beneficial molecules called short-chain fatty acids, including a short-chain fatty acid called acetate. Remarkably, Prevotella and Rikenellaceae depletion leads to an 80% reduction in acetate, potentially mediating the link between age-related gut microbiome alterations and CVD.  

Diving into this gut bacteria metabolite framework, Beer and team tested the effect of sodium acetate, the salt form of acetate, on the aortas of mice harboring Clostridium. Astonishingly, they found that acetate supplementation mitigated the aortic senescence and dysfunction. In this way, the researchers at least partially restored the protective cardiovascular effects of beneficial gut bacteria like Prevotella and Rikenellaceae. 

Sodium Acetate Elevates NAD+ and Activates Sirtuin-1   

Most of our cells are susceptible to entering senescence, which is triggered by cellular stressors like inflammation, DNA damage, and oxidative stress. Oxidative stress is caused by the excessive buildup of oxidants, which are generated by dysfunctional mitochondria. Beer and team found that exposing inner artery cells — endothelial cells (ECs) — to PAA induced mitochondrial dysfunction, subsequently leading to oxidative stress and EC senescence. 

However, sodium acetate improved mitochondrial function, preventing oxidative stress and senescence. Moreover, acetate increased NAD+ levels, a known fuel source for sirtuin-1 (Sirt1), which is a master regulator of genes involved in DNA repair and metabolism. Indeed, acetate was also shown to double Sirt1 activity. Both elevating NAD+ and activating Sirt1 have been shown to reduce mitochondrial dysfunction and diminish oxidative stress, suggesting their role in counteracting PAA-induced EC senescence.

Harnessing the Gut Microbiome’s Anti-Aging Effects 

While sodium acetate can be found in supplement form, there is a lack of studies testing the effects of sodium acetate on healthy adults. A more scientifically-backed method for improving circulating acetate and other short-chain fatty acid levels is improving overall gut microbiome health. This can be achieved by consuming around 30 grams per day of fiber, which can be found in fruits, vegetables, legumes, seeds, nuts, and whole grains. Fiber intake can reduce the risk of chronic diseases like CVD, including by reducing cholesterol levels. Prebiotic supplements, which are fiber isolates, are also available. Additionally, probiotics can be taken in supplement form or from fermented foods such as yogurt, kimchi, and some cheeses.